Melatonin is a natural hormone primarily released by the pineal gland that regulates the sleep-wake cycles. The diverse biological applications of melatonin, together with the need to develop new melatoninergic ligands, have stimulated the preparation of a wide range of melatonin derivatives. Here, all the synthetic approaches to indole-based melatonin analogues as well as their biological applications are reviewed. The modifications which have been performed on the melatonin's indole ring and the effects of these modifications on the biological activities have been analysed, detailing the binding affinity of the derivatives for melatonin receptors.